Understanding the basic neural mechanisms underlying stuttering is widely acknowledged as fundamental to informed diagnosis and treatment. The required cornerstone for this important knowledge is a theoretical framework of stuttering that accounts for various primary and associated speech characteristics and that is consistent with empirically-verified models of sensorimotor control and neural functioning. The research program proposed here takes a comprehensive neurobiological approach to explaining the neural basis of stuttering through an integrated series of theoretically-motivated, hypothesis-driven experiments. Parallel psychophysical (kinematics, sensorimotor adaptation, mechanical/sensory perturbations) and neuroimaging (fMRI) experiments will be conducted to address selected aspects of speech sensorimotor control that, according to our theoretical framework, may be implicated in stuttering. Specific aims of the series of experimental studies are to investigate in individuals who do vs. who do not stutter (a) the ability to acquire and consolidate neural representations (i.e., internal models) of the mappings between central motor commands to the vocal tract musculature and the sensory consequences of those actions, (b) the efficiency of integrating auditory and kinesthetic afferent signals into both the feedforward and feedback components of speech sensorimotor control, and (c) the activation time course and functional connectivity of the neural substrates underlying speech production. This is a collaborative program of research by scientists who have overlapping as well as complementary areas of expertise and who direct research groups using state-of-the-art instrumentation at two performance sites. Combining the expertise and resources from these sites will allow innovative investigations of the sensorimotor systems of stuttering and nonstuttering children and adults at behavioral, physiological, and neural levels of operation. These in-depth studies have the potential to inform on the development and state of the speech motor control system in individuals who stutter, and to suggest new directions for research and clinical management. Thus, this work's direct relevance to public health lies in its contributions to understanding the neural mechanisms underlying stuttering and-by generating such new insights-facilitating the development of improved approaches to diagnosis and treatment.